Ammonium Chloride → 1-(4-Bromo-2-fluorophenyl)cyclopropan-1-ol

Temperature

-78 °C

To a stirred solution of Ti(OiPr)4 (44.68 mL, 141.63 mmol, 1 eq) in diethyl ether (250 mL) was added freshly prepared ethyl magnesium iodide (212.44 mL, 424.89 mmol, 3 eq) in diethyl ether (220 mL) at −78° C. for 45 min. The reaction mixture was stirred for 90 min at −78° C., then methyl 4-bromo-2-fluorobenzoate (33.0 g, 141.63 mmol, 1.0 eq) was added and the mixture allowed to stir at RT for 16 h. Saturated aqueous NH4Cl (30 mL) was added and the mixture passed through celite pad. The ether layer was separated, washed with 1 N HCl (250 mL), brine (500 mL), water (750 mL), dried over MgSO4 and the solvent evaporated. The resulting residue was purified by CC using PE/EtOAc (19:1) as eluent to get 1-(4-bromo-2-fluorophenyl)cyclopropanol (9.01 g, 28%; TLC system: PE/EtOAc (9:1), Rf: 0.3).

1. stirringto stir at RT for 16 h
2. customThe ether layer was separated
3. washwashed with 1 N HCl (250 mL), brine (500 mL), water (750 mL)
4. dry with materialdried over MgSO4
5. customthe solvent evaporated
6. customThe resulting residue was purified by CC

ORD record

ord-d3e02c0a2c4046c386ea68452455d3ad

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946204B2